MILLER, MF*; OKADA, R; ITO, Y; DE GROEF, B; YAMAMOTO, K; DENVER, RJ; KIKUYAMA, S; University of Michigan, Ann Arbor; Waseda University, Tokyo ; Waseda University, Tokyo ; Catholic University of Leuven, Leuven; Waseda University, Tokyo ; University of Michigan, Ann Arbor; Waseda University, Tokyo : Involvement of the corticotropin-releasing factor (CRF) type 2 receptor in CRF-induced thyrotropin release from the tadpole pituitary.

Corticotropin-releasing factor (CRF) is considered to be the primary hypophysiotropin for corticotropin (ACTH) in vertebrates. In non-mammalian species, CRF induces thyroid-stimulating hormone (TSH) secretion by the anterior pituitary. Recent studies in the chicken (Gallus gallus) showed that CRF-induced TSH secretion is mediated by the type 2 CRF receptor (CRF2). Based on these results we hypothesized that TSH secretion by the tadpole pituitary is mediated by the CRF2 receptor. Using dispersed bullfrog (Rana catesbeiana) anterior pituitary cells in culture we found that CRF, Xenopus laevis urocortin 1 (xUCN1), mouse urocortin 2 (mUCN2), X. laevis urocortin 3 (xUCN3), and sauvagine (SVG) all markedly enhanced the release of immunoassayable TSH. The CRF-induced TSH release was completely blocked by the general CRF receptor antagonist astressin and by the CRF2 receptor specific antagonist antisauvagine-30; whereas, the type 1 CRF receptor specific antagonist antalarmin had no effect on TSH release. Injection of CRF, xUCN1, xUCN3 or SVG into Gosner stage 36-37 tadpoles of Spea hammondii caused rapid (by 2 hr) and robust increases in plasma thyroxine concentrations. We also found that chronic injection of the CRF2 specific agonists xUCN3, mUCN2 or mUCN3 accelerated metamorphosis of Spea hammondii as measured by hind limb growth and development. Taken together, our data support the hypothesis that TSH release (and therefore tadpole metamorphosis) is mediated by the CRF2 receptor (supported by NSF grant IBN 0235401 to R.J.D.)